This project is designed to define the role the immune system plays in the host's interaction with antigens in the intestinal tract. One major focus of our studies is investigating the induction and mechanisms of regulation of the immune response to polysaccharide antigens, such as those found in bacterial capsular materials. Using the bacterial polysaccharide dextran B1355, we have demonstrated the presence of an IgA anti-alpha(1,3) dextran B1355 antibody response in BALB/c mice that is highly age-dependent and T-cell dependent. Inasmuch as immune responses to polysaccharide antigens traditionally have been thought to be thymus-independent and largely confined to the IgM and possibly a minor IgG subclass (i.e., IgG3), our important new finding mandates a reevaluation of how the immune response to polysaccharide antigens are regulated, and may have particular relevance for mucosal immunity. The second major focus of our studies relates to the genetic regulation of the immune response to wheat gliadins, proteins known to cause the human disease Gluten-Sensitive Enteropathy (Celiac Sprue). Our studies have shown that the T-dependent antibody response to A-gliadin, a protein known to cause disease in man, can be mapped to the major histocompatibility complex (H-2) in mice. This finding in mice establishes a clear linkage between the major histocompatibility complex and the regulation of the immune response to a protein capable of causing human disease.